Glucagon like-peptide-1-(7, 36)-amide (GLP-1) suppresses glucagon release and increases the early phase of insulin secretion. However, it is currently controversial as to whether GLP-1 alters insulin sensitivity. Although it is well established that glucagon like-peptide-1-(7,36)-amide (GLP-1) is a potent stimulator of insulin secretion, its effects on insulin action and glucose effectiveness are less clear. To determine whether GLP-1 increases insulin action and glucose effectiveness, subjects with type 2 diabetes were studied on two occasions. Insulin was infused during the night on both occassions to ensure that baseline glucose concentrations were comparable. On the morning of the study, either GLP-1 (1.2 pmol/kg/min) or saline were infused along with somatostatin and replacement amounts of glucagon. Glucose was also infused in a pattern mimicking that typically observed following a carbohydrate meal while insulin concentrations were kept constant at basal levels. The increase in glucose concentration was virtually identical on the GLP-1 and saline study days during the basal (1.21 +/- 0.15 vs. 1.32 +/- 0.19 Mol/L per 6 hrs) insulin infusions. Suppression of endogenous glucose production also was comparable on the GLP-1 and saline study days during the basal (-2.7 +/- 0.3 vs. -3.1 +/- 0.2 umol/kg) insulin infusions. Stimulation of glucose uptake in the presence or absence of GLP-1 was similar during the basal (2.2 +/- 0.2 vs. 1.8 +/- 0.1 mmol/kg) insulin infusion. We conclude that when insulin and glucagon concentrations are matched, GLP-1 does not enhance glucose-induced stimulation of glucose uptake, glucose-induced suppression of glucose production. In addition, GLP-1 does not alter insulin action in people with type 2 diabetes.